Abstract: There remains a lack of prospective and controlled research on the behavioral, toxicological, and physiological effects of electronic cigarettes (ECs) to help the public health community come to a clear and accurate consensus on their risk-benefit. Moreover, the studies that have been completed used various commercially available ECs, e-liquid flavors, and nicotine concentrations, many of which are unavailable today and for which we know very little about, making the generalizability and comparisons between past, present, and future studies very difficult. The recent development of the NIDA Standard Research E-cigarette (SREC), will provide researchers the ability to address this research gap with a product that has been fully characterized, delivers nicotine efficiently, and will remain unchanged and available for an extended period of time. The present funding opportunity (PAR-17-156) is meant to begin to evaluate, with a high degree of fidelity, ECs as a potential means of reducing smoking-related risks and to provide information on the use and effects of the NIDA SREC; it is also meant to do so quickly (two-year study). In order to successfully execute the proposed study, we plan to recruit and enroll recent smoking cessation treatment failures from a state quitline (QL), which predominately serves priority populations (e.g., low socioeconomic status, high levels of mental health conditions). QLs provide ready access to a large number of tobacco users, as well as infrastructure for delivering and testing study interventions quickly. With a two-year time window, QLs are potentially the best real-world platform to quickly and with sufficient statistical power, meaningfully examine smokers' ability and willingness to switch to the SREC, and its impact on their tobacco use behaviors, nicotine dependence, and health. The proposed study will randomly assign 372 smokers who were recent QL treatment failures to a) nicotine SREC; b) placebo SREC; or c) no-product, assessment-only control (AOC). All participants will receive three calls from QL coaches (SREC education calls for SREC participants and attention-placebo calls for AOC participants). SRECs will be provided at no cost for 8 weeks, and the final follow-up will occur 12-weeks post baseline. Our specific aims are to evaluate 1) provision of nicotine SREC vs. placebo SREC on product switching/substitution, craving/withdrawal, abuse liability, number of cigarettes smoked, and perceived nicotine dependence; 2) changes in biomarkers of tobacco constituent exposure and physiological effects; and 3) which EC device characteristics and effects (e.g., satisfaction, ?throat hit?, craving reduction) influence complete (vs. partial or no) switching.